Sequence Architecture Research Articles

Evolution of Copolymers of Epoxides and CO2: Catalysts, Monomers, Architectures, and Applications.

The copolymerization of CO2 and epoxides presents a transformative approach to converting greenhouse gases into aliphatic polycarbonates (CO2-PCs), thereby reducing the polymer industry's dependence on fossil resources. Over the past 50 years, a wide array of metallic catalysts, both heterogeneous and homogeneous, have been developed to achieve precise control over polymer selectivity, sequence, regio-, and stereoselectivity. This review details the evolution of metal-based catalysts, with a particular focus on the emergence of organoborane catalysts, and explores how these catalysts effectively address kinetic and thermodynamic challenges in CO2/epoxides copoly2merization. Advances in the synthesis of CO2-PCs with varied sequence and chain architectures through diverse polymerization protocols are examined, alongside the applications of functional CO2-PCs produced by incorporating different epoxides. The review also underscores the contributions of computational techniques to our understanding of copolymerization mechanisms and highlights recent advances in the closed-loop chemical recycling of CO2-sourced polycarbonates. Finally, the industrialization efforts of CO2-PCs are discussed, offering readers a comprehensive understanding of the evolution and future potential of epoxide copolymerization with CO2.

Current Updates of CRISPR/Cas System and Anti-CRISPR Proteins: Innovative Applications to Improve the Genome Editing Strategies.

The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated sequence (CRISPR/Cas) system is a cutting-edge genome-editing tool employed to explore the functions of normal and disease-related genes. The CRISPR/Cas system has a remarkable diversity in the composition and architecture of genomic loci and Cas protein sequences. Owing to its excellent efficiency and specificity, this system adds an outstanding dimension to biomedical research on genetic manipulation of eukaryotic cells. However, safe, efficient, and specific delivery of this system to target cells and tissues and their off-target effects are considered critical bottlenecks for the therapeutic applications. Recently discovered anti-CRISPR proteins (Acr) play a significant role in limiting the effects of this system. Acrs are relatively small proteins that are highly specific to CRISPR variants and exhibit remarkable structural diversity. The in silico approaches, crystallography, and cryo-electron microscopy play significant roles in elucidating the mechanisms of action of Acrs. Acrs block the CRISPR/Cas system mainly by employing four mechanisms: CRISPR/Cas complex assembly interruption, target-binding interference, target cleavage prevention, and degradation of cyclic oligonucleotide signaling molecules. Engineered CRISPR/Cas systems are frequently used in gene therapy, diagnostics, and functional genomics. Understanding the molecular mechanisms underlying Acr action may help in the safe and effective use of CRISPR/Cas tools for genetic modification, particularly in the context of medicine. Thus, attempts to regulate prokaryotic CRISPR/Cas surveillance complexes will advance the development of antimicrobial drugs and treatment of human diseases. In this review, recent updates on CRISPR/Cas systems, especially CRISPR/Cas9 and Acrs, and their novel mechanistic insights are elaborated. In addition, the role of Acrs in the novel applications of CRISPP/Cas biotechnology for precise genome editing and other applications is discussed.

Dissection of core promoter syntax through single nucleotide resolution modeling of transcription initiation.

How the DNA sequence of cis-regulatory elements encode transcription initiation patterns remains poorly understood. Here we introduce CLIPNET, a deep learning model trained on population-scale PRO-cap data that predicts the position and quantity of transcription initiation with single nucleotide resolution from DNA sequence more accurately than existing approaches. Interpretation of CLIPNET revealed a complex regulatory syntax consisting of DNA-protein interactions in five major positions between -200 and +50 bp relative to the transcription start site, as well as more subtle positional preferences among transcriptional activators. Transcriptional activator and core promoter motifs work non-additively to encode distinct aspects of initiation, with the former driving initiation quantity and the latter initiation position. We identified core promoter motifs that explain initiation patterns in the majority of promoters and enhancers, including DPR motifs and AT-rich TBP binding sequences in TATA-less promoters. Our results provide insights into the sequence architecture governing transcription initiation.

Impact of Process Sequence and Device Architecture on Mechanical Stress and Electrical Properties of 3-D Nand Flash

Impact of Process Sequence and Device Architecture on Mechanical Stress and Electrical Properties of 3-D Nand Flash

Genome divergence and reproductive incompatibility among populations of Ganaspis near brasiliensis.

During the last decade, the spotted wing drosophila, Drosophila suzukii, has spread from eastern Asia to the Americas, Europe, and Africa. This fly attacks many species of cultivated and wild fruits with soft, thin skins, where its serrated ovipositor allows it to lay eggs in undamaged fruit. Parasitoids from the native range of D. suzukii may provide sustainable management of this polyphagous pest. Among these parasitoids, host-specificity testing has revealed a lineage of Ganaspis near brasiliensis, referred to in this paper as G1, that appears to be a cryptic species more host-specific to D. suzukii than other parasitoids. Differentiation among cryptic species is critical for introduction and subsequent evaluation of their impact on D. suzukii. Here, we present results on divergence in genomic sequences and architecture and reproductive isolation between lineages of Ganaspis near brasiliensis that appear to be cryptic species. We studied five populations, two from China, two from Japan, and one from Canada, identified as the G1 vs G3 lineages based on differences in cytochrome oxidase l sequences. We assembled and annotated the genomes of these populations and analyzed divergences in sequence and genome architecture between them. We also report results from crosses to test reproductive compatibility between the G3 lineage from China and the G1 lineage from Japan. The combined results on sequence divergence, differences in genome architectures, ortholog divergence, reproductive incompatibility, differences in host ranges and microhabitat preferences, and differences in morphology show that these lineages are different species. Thus, the decision to evaluate the lineages separately and only import and introduce the more host-specific lineage to North America and Europe was appropriate.

Variability of sequence architecture in a rift margin controlled by tectonic activity: The Eocene Dongying Depression, Bohai Bay Basin, China

AbstractSequence architectures along the margins of rift basins are still poorly documented compared to passive continental margin settings. The Eocene Shahejie Formation on the rift margin of the Dongying Depression records a complex sequence stratigraphic distribution of conglomerate, sandy conglomerate, sandstone and mudstone. These facies have been mainly attributed to fan delta and marginal subaqueous fan depositional settings that developed during segmented fault activity along the rift margin. We utilize three‐dimensional (3D) seismic data, conventional cores, and wireline log data to dissect the overall wedge‐shaped upper sub‐member strata of the Shahejie Formation's fourth member. The study interval is a third‐order sequence formed between 45.4 and 42.5 Ma and contains a lowstand–transgressive systems tract (LST–TST) and a highstand systems tract–falling‐stage systems tract (HST–FSST). We found that the LST–TST developed several huge amalgamated depocenters along the Chennan border fault; whereas, these depocenters gradually diminished or even disappeared during the HST–FSST period, illustrating less significant control by the border fault. Through calculations of strata growth rates, we confirmed that the segmented activity of the border fault influences the stratigraphic distribution and facies evolution during these two periods. Specifically, deep‐water depositional systems, represented by marginal subaqueous fans were widely developed in the LST–TST period and were influenced by overall strong tectonic activity, including retrogradational (R) and aggradational (A) patterns. However, the aggradational to progradational (AP) deltas and progradational to degradational (PD) deltas dominated the generally muted tectonic activity setting during the HST–FSST. Additionally, influenced by localized segmented fault activity, these systems tracts exhibit incomplete vertical development, resulting in spatial variability in stratigraphic stacking patterns.

A bird's-eye view: exploration of the flavin-containing monooxygenase superfamily in common wheat.

The Flavin Monooxygenase (FMO) gene superfamily in plants is involved in various processes most widely documented for its involvement in auxin biosynthesis, specialized metabolite biosynthesis, and plant microbial defense signaling. The roles of FMOs in defense signaling and disease resistance have recently come into focus as they may present opportunities to increase immune responses in plants including leading to systemic acquired resistance, but are not well characterized. We present a comprehensive catalogue of FMOs found in genomes across vascular plants and explore, in depth, 170 wheat TaFMO genes for sequence architecture, cis-acting regulatory elements, and changes due to Transposable Element insertions. A molecular phylogeny separates TaFMOs into three clades (A, B, and C) for which we further report gene duplication patterns, and differential rates of homoeologue expansion and retention among TaFMO subclades. We discuss Clade B TaFMOs where gene expansion is similarly seen in other cereal genomes. Transcriptome data from various studies point towards involvement of subclade B2 TaFMOs in disease responses against both biotrophic and necrotrophic pathogens, substantiated by promoter element analysis. We hypothesize that certain TaFMOs are responsive to both abiotic and biotic stresses, providing potential targets for enhancing disease resistance, plant yield and other important agronomic traits. Altogether, FMOs in wheat and other crop plants present an untapped resource to be exploited for improving the quality of crops.

Interpretable prediction of mRNA abundance from promoter sequence using contextual regression models.

While machine learning models have been successfully applied to predicting gene expression from promoter sequences, it remains a great challenge to derive intuitive interpretation of the model and reveal DNA motif grammar such as motif cooperation and distance constraint between motif sites. Previous interpretation approaches are often time-consuming or have difficulty to learn the combinatory rules. In this work, we designed interpretable neural network models to predict the mRNA expression levels from DNA sequences. By applying the Contextual Regression framework we developed, we extracted weighted features to cluster samples into different groups, which have different gene expression levels. We performed motif analysis in each cluster and found motifs with active or repressive regulation on gene expression. By comparing the co-occurrence locations of discovered motifs, we also uncovered multiple grammars of motif combination including communities of cooperative motifs and distance constraints between motif pairs. These results revealed new insights of the regulatory architecture of promoter sequences.

Deviation Sequence Neural Network Control for Path Tracking of Autonomous Vehicles

Despite its excellent performance in path tracking control, the model predictive control (MPC) is limited by computational complexity in practical applications. The neural network control (NNC) is another attractive solution by learning the historical driving data to approximate optimal control law, but a concern is that the NNC lacks security guarantees when encountering new scenarios that it has never been trained on. Inspired by the prediction process of MPC, the deviation sequence neural network control (DS-NNC) separates the vehicle dynamic model from the approximation process and rebuilds the input of the neural network (NN). Taking full use of the deviation sequence architecture and the real-time vehicle dynamic model, the DS-NNC is expected to enhance the adaptability and the training efficiency of NN. Finally, the effectiveness of the proposed controller is verified through simulations in Matlab/Simulink. The simulation results indicate that the proposed path tracking NN controller possesses adaptability and learning capabilities, enabling it to generate optimal control variables within a shorter computation time and handle variations in vehicle models and driving scenarios.

The architecture of basalt reservoirs in the North Atlantic Igneous Province with implications for basalt carbon sequestration

Abstract Offshore CO 2 sequestration in basaltic formations of the North Atlantic Igneous Province may allow permanent storage of large volumes of CO 2 through rapid carbonate mineralization. Characterizing the internal architecture of such reservoirs is key to assessing the storage potential. In this study, six photogrammetry models and three boreholes on the Faroe Islands have been used to characterize the internal lava sequence architectures as a direct analogue to potential offshore North Atlantic Igneous Province storage sites. The studied formations are dominated by c. 5 to 50 m thick simple and compound lava flows, with drill core observations documenting a transition from pāhoehoe moving towards ‘a’ā lava flow types interbedded with thin (<5 m thick) volcaniclastic rock units. The identification of flow margin breccias is potentially important as these units form excellent reservoirs in several other localities globally. Stacked, thick simple flows may present sealing units associated with dense flow interiors. Connected porous and permeable lava flow crusts present potential reservoirs; however, the degree of secondary mineralization and alteration can alter initially good reservoir units to impermeable barriers for fluid flow. Large-scale reservoir volumes may be present mainly within both vesicular, fractured pāhoehoe and brecciated flow margins of transitional simple lava flows.

Tectono-stratigraphic evolution in the Paleocene Lishui Sag, East China Sea Shelf Basin

The tectonic evolution of the Lishui Sag in the East China Sea Shelf Basin significantly influences its sequence stratigraphy. By integrating seismic reflections, well logs and core data, this study examines the quantitative activity of the Lingfeng fault, sequence framework and sequence architecture in the Lishui Sag. The Paleocene succession is divided into one second-order sequence (SSQ1), three third-order sequences (SQ1–SQ3) and nine system tracts, representing a complete syn-rift evolution consisting of initial syn-rift, rift climax and late syn-rift stages. The results indicate that the differential activity of the Lingfeng fault shapes the basin structure and controls the subsidence centre, leading to prominent variations in the spatial distribution and filling of the sequence stratigraphy during different tectonic stages. The initial syn-rift sequence (SQ1), characterised by a low activity of the segmented Lingfeng fault, is primarily found in isolated small sub-sags. The rift climax sequence (SQ2), with increasing displacement and longer segmented fault zones, exhibits a wedge-shaped filling pattern with substantial topographic elevation differences. The late syn-rift sequence (SQ3) shows a gradual decrease in tectonic activity and uniform filling, with all system tracts within the sequences fully developed. The sequence architecture of the hanging wall in the Lishui Sag can be classified into fault-scarp and fault-slope type, whereas the sequence architecture of the hanging wall dip-slope can be classified into sedimentary slope-break and faulted slope-break.

CANDy: Automated analysis of domain architectures in carbohydrate-active enzymes.

Carbohydrate-active enzymes (CAZymes) can be found in all domains of life and play a crucial role in metabolic and physiological processes. CAZymes often possess a modular structure, comprising not only catalytic domains but also associated domains such as carbohydrate-binding modules (CBMs) and linker domains. By exploring the modular diversity of CAZy families, catalysts with novel properties can be discovered and further insight in their biological functions and evolutionary relationships can be obtained. Here we present the carbohydrate-active enzyme domain analysis tool (CANDy), an assembly of several novel scripts, tools and databases that allows users to analyze the domain architecture of all protein sequences in a given CAZy family. CANDy's usability is shown on glycoside hydrolase family 48, a small yet underexplored family containing multi-domain enzymes. Our analysis reveals the existence of 35 distinct domain assemblies, including eight known architectures, with the remaining assemblies awaiting characterization. Moreover, we substantiate the occurrence of horizontal gene transfer from prokaryotes to insect orthologs and provide evidence for the subsequent removal of auxiliary domains, likely through a gene fission event. CANDy is available at https://github.com/PyEED/CANDy.

Identifying promoter sequence architectures via a chunking-based algorithm using non-negative matrix factorisation.

Core promoters are stretches of DNA at the beginning of genes that contain information that facilitates the binding of transcription initiation complexes. Different functional subsets of genes have core promoters with distinct architectures and characteristic motifs. Some of these motifs inform the selection of transcription start sites (TSS). By discovering motifs with fixed distances from known TSS positions, we could in principle classify promoters into different functional groups. Due to the variability and overlap of architectures, promoter classification is a difficult task that requires new approaches. In this study, we present a new method based on non-negative matrix factorisation (NMF) and the associated software called seqArchR that clusters promoter sequences based on their motifs at near-fixed distances from a reference point, such as TSS. When combined with experimental data from CAGE, seqArchR can efficiently identify TSS-directing motifs, including known ones like TATA, DPE, and nucleosome positioning signal, as well as novel lineage-specific motifs and the function of genes associated with them. By using seqArchR on developmental time courses, we reveal how relative use of promoter architectures changes over time with stage-specific expression. seqArchR is a powerful tool for initial genome-wide classification and functional characterisation of promoters. Its use cases are more general: it can also be used to discover any motifs at near-fixed distances from a reference point, even if they are present in only a small subset of sequences.

Sedimentary sequence and evolutionary characteristics of the rift system of Neoproterozoic Nanhua System and Doushantuo Formation: A case study from the northeastern margin of Sichuan Basin

Neoproterozoic strata are widely developed in the Upper Yangtze region of South China, among which the Sinian Dengying Formation has been discovered with numerous large gas fields in the Sichuan Basin, and hence they have become an essential domain for natural gas exploration and development. The early‐to‐middle Neoproterozoic Nanhua System and Doushantuo Formation are characterized by rifting deposits in the northeastern margin of Sichuan Basin, but their depositional succession and sequence architectures are still unclear, which has largely restricted our understanding of the resource potential of these strata. In this paper, based on the outcrops of the Neoproterozoic Nanhua System and Doushantuo Formation in the northeastern margin of Sichuan Basin, we describe the stratigraphic distribution and sedimentary evolutionary characteristics, and establish the regional stratigraphic framework, sedimentary cycle and evolutionary sequence of the Nanhua System and Doushantuo Formation. The results show that the lithology of the Nanhua System and Doushantuo Formation is primarily composed of conglomerate, conglomeratic sandstone, medium‐fine sandstone, siltstone, mudstone, shale and tillite; a variety of sedimentary facies including alluvial fan, river, delta, coastal shore, shelf, basin and tillite were developed; five third‐order sequences could be identified, representing multiple cycles of marine transgression and regression. The climate during the deposition of the Nanhua System and Doushantuo Formation underwent from a warm and humid pre‐glacial period through cold and arid multiple glacial periods to a warm and humid interglacial period, which consequently formed a sedimentary sequence of alluvial fan and fluvial delta to tillite during the early period, shelf basin to tillite during the middle period and slope basin to delta facies during the late period. In terms of a plan view, the depositional pattern is composed of alluvial fans and deltas at the proximal part of the rift, deep‐water shelf to slope at the middle part of the rift and slope to basin facies at the central part of the rift. Finally, we propose that large‐scale distribution of high‐quality source rocks developed in the interglacial Datangpo and Doushantuo formations, while fluvial‐deltaic reservoirs occurred in the Gucheng, Nantuo and Doushantuo formations, thus showing favourable resource potential and exploration prospects within the Sichuan Basin.

Web service embedding: Representing the invocation association between services with practical-valued vectors

Service representation using specified methods to express the service’s functionalities and non-functionalities in a machine-understandable format is crucial in service composition. In representing non-functionalities, existing approaches focus on QoS (Quality of Service) or sociability. The invocation association between services has not been considered in service representation. However, as the invocation association reflects the actual invocation situation on service execution, the inconsideration will increase the failure of service composition. Thus, finding an appropriate method to represent the invocation association is a significant issue in service composition. This paper proposes a novel service representation method called web service embedding (WSE) to generate a practical-valued vector representation using deep learning sequence models to address the challenge. First, we propose utilizing deep learning sequence models to capture the invocation association from service composition/invocation sequences. Next, the representation vectors of services can be generated using the pre-trained models by designing an unsupervised training solution. Then, two presented metrics, context invocation relevance, and semantic invocation relevance, are used to measure how well the embedding vectors of the models express the invocation association for clustering in service composition. Finally, various neural sequence architectures have been inspected to find suitable models for WSE. The experimental results show that our proposed WSE can successfully perform service representation for clustering based on the invocation association.

Decoding the Late Pleistocene-Holocene Terrace Evolution along the Main Frontal Thrust Zone, Northeastern Himalayas, India: Insights from Tectonic Geomorphology, Sedimentology, and Optical Dating

Abstract Fluvial archives are the best preserved and provide valuable means of obtaining information pertaining to climate and tectonic deformation of an area. The present study is an attempt to reconstruct the landform evolution history in the northeastern Himalayan region of India. Based on field investigation, tectonogeomorphic mapping, and OSL dating, strath and various levels of cut-and-fill terraces were investigated along the mountain front. Optically stimulated luminescence ages of the terrace sequences suggest that the valley incision occurred in three phases, at ~23 ka, ~14 ka and ~9 – 3 ka and one phase of aggradation was also identified at ~ 7 ka. The strath terraces suggest two major episodes of tectonic uplift in the region around ~ 8 ka and ~ 6 ka. This yields an uplift rate of 0.4 and 0.9 mm/yr. The result from the study suggested that the rapid rejuvenation along the mountain front led to the formation of the strath terraces with enhanced incision of the fluvial terrace and influenced the sedimentary architecture of valley fill sequences.

Chemical Evolution of Amphiphilic Xenopeptides for Potentiated Cas9 Ribonucleoprotein Delivery.

The introduction of the CRISPR/Cas9 system in the form of Cas9/sgRNA ribonucleoproteins (RNP) is an efficient, straightforward strategy for genome editing, and potent RNP carriers are in high demand. Here, we report a series of artificial peptides based on novel ionizable amino acids that are able to deliver Cas9 RNP into cells very efficiently. Systematic variation of hydrophobic properties revealed a relationship between the xenopeptide logD7.4 and genome editing potency. By correlating the physicochemical properties with biological activity, individual optima were found for different xenopeptide sequence architectures. The optimized amphiphilic carriers enable ∼88% eGFP knockout at an RNP dose of only 1 nM and up to 40% homology-directed repair (HDR) in eGFP/BFP switchable reporter cells by co-delivery with an ssDNA template. Mechanistic studies demonstrated that hydrophobically balanced xenopeptides are more resistant to ionic stress as well as concentration-dependent dissociation and promote endocytosis by both clathrin- and macropinocytosis-mediated pathways. The systematic study develops a versatile and adjustable carrier platform and highlights impactful structure-activity relationships, providing a new chemical guide for the design and optimization of nonviral Cas9 RNP nanocarriers.

Decoding polymer chains via gated inclusion into flexible nanoporous crystals

•Vinyl co-polymers are inserted in nanopores of a flexible MOF crystal •The flexible nanopores enable recognition of polymer microstructures •Monomer structure, composition, sequence, and block architecture are identified •Separation of polymers by decoding their microstructures is achieved Recognizing the microstructures of synthetic polymers remains a challenging task because there is currently no rational approach for accessing the microstructures of each polymer chain. Conversely, during protein biosynthesis, the microstructure of an RNA string is read with precision at the molecular level such that the nanospace within the ribosome serves as the workplace for highly specific molecular recognition. Herein, we report the microstructure recognition of polymers using nanopores of a flexible metal-organic framework (MOF) crystal, in which well-ordered coordination sites (open metal sites) developed in the MOF pores enable the identification of monomer species, composition, block segments, and local monomer sequence of vinyl polymers via coordination-driven impregnation. This allows for the selective adsorption of polymer chains with specific monomer structure, composition, and arrangements from a mixture of structural analogs, facilitating polymer separation and characterization for material chemistry, as well as information chemistry, by using synthetic polymers as data sources. Recognizing the microstructures of synthetic polymers remains a challenging task because there is currently no rational approach for accessing the microstructures of each polymer chain. Conversely, during protein biosynthesis, the microstructure of an RNA string is read with precision at the molecular level such that the nanospace within the ribosome serves as the workplace for highly specific molecular recognition. Herein, we report the microstructure recognition of polymers using nanopores of a flexible metal-organic framework (MOF) crystal, in which well-ordered coordination sites (open metal sites) developed in the MOF pores enable the identification of monomer species, composition, block segments, and local monomer sequence of vinyl polymers via coordination-driven impregnation. This allows for the selective adsorption of polymer chains with specific monomer structure, composition, and arrangements from a mixture of structural analogs, facilitating polymer separation and characterization for material chemistry, as well as information chemistry, by using synthetic polymers as data sources.

Reconstruction of Tournaisian-Viséan tectonic and climatically induced event histories of the Mobarak carbonate platform along depositional strike in the northeastern margin of Gondwana: Constraints from high-resolution cycle and sequence stratigraphy

Cyclic successions are one of the most important types of deposits in the carbonate platform of the Mississippian (Tournaisian-Viséan) in Gondwanan and Laurussian margins. The importance of climatically induced events impact on the amplitudes and frequencies of sea-level fluctuations in Mississippian of Iran is significant because the beginning, extent, duration, and significance of periods of climatically induced events in northern margin of Gondwana are not well recognized. A high-resolution sequence architecture in integration with paleoenvironmental reconstruction and foraminiferal biozonation from the Tournaisian-early Visean carbonate successions of the Mobarak Formation in Alborz basin along depositional strike (E-W- a distance of c. 340 km) suggests a mosaic-like pattern of deposition and compartmentalization of the depositional settings (homocline ramp to distally steepened ramp). According to the recognized facies, the stacking pattern of high-frequency cycles across the platform, and major accommodation events recognized on the correlated Fischer plots, six 3rd-order sequences (DS1–DS6) were identified. Detailed analysis on high-frequency cycles representing a highly variable number of shallowing-upward cycles, types, thicknesses, and facies heterogeneity along depositional strike. A combination of the episodic tectonic events along faults interacting with autocyclic processes, and inherited topographic irregularities are suggested as the driving mechanism for the cycle development. Six stages of Mobarak carbonate platform evolution based on understand the interplay of autocyclic and allocyclic controls are recognized in a hierarchical 3rd-order sequence stratigraphic framework and a chronological order: (1) early Hastarian corresponds to post-glacial transgressive episode with progressive backstepping of facies belts of early TST of DS1 throughout the region; (2) middle to late Hastarian corresponds to a major transgressional phase of DS1 following global temperature rise superimposed on different subsidence/uplift rates with the deformation of the platform along depositional strike; (3) Hastarian–Ivorian boundary corresponds to TST of DS2 with facies heterogeneity along depositional strike related to continuation of different subsidence/uplift rates. The absence of any systematic changes in the amplitude and period of cyclicity or lowstand deposits and subaerial surfaces during this phase shows the lack of influence of mid-Tournaisian glaciation and concurrent eustatic regression in northern margin of Gondwana. (4) early to middle Ivorian coincides with the RST of DS2 and TST of DS3 showing by remarkable topographic irregularities in the basin physiography and change in the position of the depocenter axis from a E–W trend to the center; (5) late Ivorian-early Moliniacian coincides with the RST of DS3 and DS4 showing by the Late Tournaisian thermal period and eustatic rise superimposed on uplift and subaerial exposure of the western part and subsidence in the central and eastern parts of the basin; (6) Moliniacian coincides with DS5-DS6 sequences showing by change from fault-related topography to major tilted fault-block topography accompanied by eustatic sea-level fall caused indirectly by the Viséan and Serpukhovian glaciations phases.

Integrated single-nucleus sequencing and spatial architecture analysis identified distinct injured-proximal tubular types in calculi rats

BackgroundUrolithiasis with high prevalence and recurrence rate, has impacts on kidney injury in patients, becomes a socioeconomic and healthcare problem in worldwide. However, the biology of kidney with crystal formation and proximal tubular injury remains essentially unclear. The present study aims to evaluate the cell biology and immune-communications in urolithiasis mediated kidney injury, to provide new insights in the kidney stone treatment and prevention.ResultsWe identified 3 distinct injured-proximal tubular cell types based on the differentially expression injury markers (Havcr1 and lcn2) and functional solute carriers (slc34a3, slc22a8, slc38a3 and slc7a13), and characterized 4 main immune cell types in kidney and one undefined cell population, where F13a1+/high/CD163+/high monocyte & macrophage and Sirpa/Fcgr1a/Fcgr2a+/high granulocyte were the most enriched. We performed intercellular crosstalk analysis based on the snRNA-seq data and explored the potential immunomodulation of calculi stone formation, and founded that the interaction between ligand Gas6 and its receptors (Gas6-Axl, Gas6-Mertk) was specifically observed in the injured-PT1 cells, but not injured-PT2 and -PT3 cells. The interaction of Ptn-Plxnb2 was only observed between the injured-PT3 cells and its receptor enriched cells.ConclusionsPresent study comprehensively characterized the gene expression profile in the calculi rat kidney at single nucleus level, identified novel marker genes for all cell types of rat kidney, and determined 3 distinct sub-population of injured-PT clusters, as well as intercellular communication between injured-PTs and immune cells. Our collection of data provides a reliable resource and reference for studies on renal cell biology and kidney disease.